title: A role for decorin in a murine model of allergen-induced asthma.
abstract: Decorin (Dcn) is an extracellular matrix proteoglycan, which affects airway mechanics, airway-parenchymal interdependence, airway smooth muscle proliferation and apoptosis, and transforming growth factor-β bioavailability. As Dcn deposition is differentially altered in asthma, we questioned whether Dcn deficiency would impact the development of allergen-induced asthma in a mouse model. Dcn(-/-) and Dcn(+/+) mice (C57Bl/6) were sensitized with ovalbumin (OA) and challenged intranasally 3 days/wk × 3 wk. After OA challenge, mice were anesthetized, and respiratory mechanics measured under baseline conditions and after delivery of increasing concentrations of methacholine aerosol. Complex impedance was partitioned into airway resistance and tissue elastance and damping. Bronchoalveolar lavage was performed. Lungs were excised, and tissue sections evaluated for inflammatory cell influx, α-smooth muscle actin, collagen, biglycan, and Dcn deposition. Changes in TH-2 cytokine mRNA and protein were also measured. Airway resistance was increased in OA-challenged Dcn(+/+) mice only (P < 0.05), whereas tissue elastance and damping were increased in both OA-challenged Dcn(+/+) and Dcn(-/-), but more so in Dcn(+/+) mice (P < 0.001). Inflammation and collagen staining within the airway wall were increased with OA in Dcn(+/+) only (P < 0.001 and P < 0.01, respectively, vs. saline). IL-5 and IL-13 mRNA were increased in lung tissue of OA-challenged Dcn(+/+) mice. Dcn deficiency resulted in more modest OA-induced hyperresponsiveness, evident at the level of the central airways and distal lung. Differences in physiology were accompanied by differences in inflammation and remodeling. These findings may be, in part, due to the well-described ability of Dcn to bind transforming growth factor-β and render it less bioavailable.
authors.affiliation: Meakins-Christie Laboratories, McGill University Health Center, Montreal, Quebec, Canada.
authors.forename: Cinzia L
authors.initials: CL
authors.lastname: Marchica
authors.forename: Valentina
authors.initials: V
authors.lastname: Pinelli
authors.forename: Marcos
authors.initials: M
authors.lastname: Borges
authors.forename: Jaryd
authors.initials: J
authors.lastname: Zummer
authors.forename: Venkatesan
authors.initials: V
authors.lastname: Narayanan
authors.forename: Renato V
authors.initials: RV
authors.lastname: Iozzo
authors.forename: Mara S
authors.initials: MS
authors.lastname: Ludwig
mesh_terms: D000403:Airway Resistance / Q000276:immunology; D000485:Allergens / Q000009:adverse effects*; D000818:Animals; D001249:Asthma / Q000139:chemically induced* / Q000378:metabolism*; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D058575:Decorin / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007124:Immunoenzyme Techniques; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000008:administration & dosage; D012333:RNA, Messenger / Q000235:genetics; D012137:Respiratory System / Q000187:drug effects / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000485:Allergens; D016207:Cytokines; C546879:Dcn protein, mouse; D058575:Decorin; D012333:RNA, Messenger; D010047:Ovalbumin